<p>Mechanistic research holds promise for bacterial vaccines and phage therapies for <em>Pseudomonas aeruginosa</em></p>

Abstract

Vaccines for Pseudomonas aeruginosa have been of longstanding interest to immunologists, bacteriologists, and clinicians, due to the widespread prevalence of hospitalacquired infection. As P. aeruginosa becomes increasingly antibiotic resistant, there is a dire need for novel treatments and preventive vaccines. Despite intense efforts, there currently remains no vaccine on the market to combat this dangerous pathogen. This article summarizes current and past vaccines under development that target various constituents of P. aeruginosa. Targeting lipopolysaccharides and O-antigens have shown some promise in preventing infection. Recombinant flagella and pili that target TLR5 have been utilized to combat P. aeruginosa by blocking its motility and adhesion. The type 3 secretion system components, such as needle-like structure PcrV or exotoxin PopB, are also potential vaccine targets. Outer membrane proteins including OprF and OprI are newer representatives of vaccine candidates. Live attenuated vaccines are a focal point in this review, and are also considered for novel vaccines. In addition, phage therapy is revived as an effective option for treating refractory infections after failure with antibiotic treatment. Many of the aforementioned vaccines act on a single target, thus lacking a broad range of protection. Recent studies have shown that mixtures of vaccines and combination approaches may significantly augment immunogenicity, thereby increasing their preventive and therapeutic potential.

The Role of Pseudomonas aeruginosa Lipopolysaccharide in Bacterial Pathogenesis and Physiology

“…The generation of therapeutics that inhibit the Lipid A modification pathways will be indispensable to mitigating CAMP resistance, while the continued characterization of "natural" antimicrobials that use LPS as a receptor, such as phages and bacteriocins, may be an effective way to develop targeted therapeutics. Finally, although LPS-based P. aeruginosa vaccines had only limited success in the past [199], this may still prove to be a promising prophylactic treatment since the use of OMVs and recombinant bacterial glycosylation pathways to produce glycoconjugates has made these vaccines safer, more effective, and cheaper to produce [200].…”

The Landscape of Pseudomonas aeruginosa Membrane-Associated Proteins

“…In agreement with these findings, the potential antigenicity of nine outer membrane proteins, including several outer membrane porins, emerged fron our study. Some combination of these proteins, including OprF and OprI [48], or OprF and OprL [49], are currently investigated as vaccine candidates. Similarly, PA0833 was demonstrated is an OmpA C-like protein that induces a protective immune response in mice, indicating it as a promising antigen for vaccine development [50].…”

Bacteriophages inhibit biofilms formed by multi-drug resistant bacteria isolated from septic wounds

“…Contrary to the planktonic bacterial cells, pathogenic bacterial communities in the extracellular matrix usually exhibit distinct features such as:: a) intercellular signals between the community (quorum sensing) (Sharma et al, 2016), which regulates the maturation and detachment of the biofilms; b) activation of secondary messengers, which plays a role in the formation of biofilms, flagellar movements and production of extracellular polysaccharides (Hoggarth et al, 2019) and c) expression of DNA-binding proteins, amyloid and amyloid-like proteins, Biofilm Associated Proteins (Bap), and critical proteins which play a significant role in the establishment of the matrix association for the bacteria to encase in biofilms (Zhu et al, 2002; Le et al, 2013; Gondil and Chhibber, 2018; Schiffer et al, 2019). Formation of biofilms depends on both internal and external factors such as moist surface, energy source at the wound site, type of bacterial interaction, availability of receptors on bacteria for its attachment, temperature, pH and other factors (Merckoll et al, 2009; Bessa et al, 2015; Zhang et al, 2018).…”